title: Structure and molecular mechanism of a nucleobase-cation-symport-1 family transporter.
abstract: The nucleobase-cation-symport-1 (NCS1) transporters are essential components of salvage pathways for nucleobases and related metabolites. Here, we report the 2.85-angstrom resolution structure of the NCS1 benzyl-hydantoin transporter, Mhp1, from Microbacterium liquefaciens. Mhp1 contains 12 transmembrane helices, 10 of which are arranged in two inverted repeats of five helices. The structures of the outward-facing open and substrate-bound occluded conformations were solved, showing how the outward-facing cavity closes upon binding of substrate. Comparisons with the leucine transporter LeuT(Aa) and the galactose transporter vSGLT reveal that the outward- and inward-facing cavities are symmetrically arranged on opposite sides of the membrane. The reciprocal opening and closing of these cavities is synchronized by the inverted repeat helices 3 and 8, providing the structural basis of the alternating access model for membrane transport.
authors.affiliation: Membrane Protein Laboratory, Diamond Light Source Limited, Harwell Science and Innovation Campus, Chilton, Didcot, Oxfordshire OX11 0DE, UK.
authors.forename: Simone
authors.initials: S
authors.lastname: Weyand
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Shimamura
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yajima
authors.forename: Shun'ichi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Osman
authors.initials: O
authors.lastname: Mirza
authors.forename: Kuakarun
authors.initials: K
authors.lastname: Krusong
authors.forename: Elisabeth P
authors.initials: EP
authors.lastname: Carpenter
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Rutherford
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Hadden
authors.forename: John
authors.initials: J
authors.lastname: O'Reilly
authors.forename: Pikyee
authors.initials: P
authors.lastname: Ma
authors.forename: Massoud
authors.initials: M
authors.lastname: Saidijam
authors.forename: Simon G
authors.initials: SG
authors.lastname: Patching
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Hope
authors.forename: Halina T
authors.initials: HT
authors.lastname: Norbertczak
authors.forename: Peter C J
authors.initials: PC
authors.lastname: Roach
authors.forename: So
authors.initials: S
authors.lastname: Iwata
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Henderson
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Cameron
mesh_terms: D000192:Actinomycetales / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002412:Cations / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D006827:Hydantoins / Q000737:chemistry / Q000378:metabolism; D017136:Ion Transport; D008958:Models, Molecular; D008969:Molecular Sequence Data; D033702:Nucleobase Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012964:Sodium / Q000378:metabolism; D027981:Symporters / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D002412:Cations; D006827:Hydantoins; D033702:Nucleobase Transport Proteins; D027981:Symporters; C031427:5-benzylhydantoin; D012964:Sodium